- Intramolecular Reductive Cyclization of o-Nitroarenes via Biradical Recombination
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A visible-light-induced/thiourea-mediated intramolecular cyclization of o-nitroarenes under mild conditions is realized for the first time, which provides an efficient and environmentally friendly way to access pharmaceutical relevant quinazolinone derivatives. The reaction can be easily extended to gram level by using a continuous-flow setup with high efficiency. Mechanistic investigation including control experiments, transient fluorescence, UV-vis spectra, and DFT calculations suggests that the formation of active biradical intermediates via intramolecular single electron transfer (SET) is key stage in the catalytic cycle.
- Lu, Cong,Su, Zhishan,Jing, Dong,Jin, Songyang,Xie, Lijuan,Li, Liangrui,Zheng, Ke
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p. 1438 - 1443
(2019/03/07)
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- Metal-Free Synthesis of Polycyclic Quinazolinones Enabled by a (NH4)2S2O8-Promoted Intramolecular Oxidative Cyclization
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An efficient metal-free, (NH4)2S2O8 mediated intramolecular oxidative cyclization for the construction of polycyclic heterocycles was disclosed. A series of polycyclic quinazolinone derivatives with good functional group tolerance were obtained in high yields. The natural products tryptanthrin and rutaecarpine, as well as their derivatives, were easily synthesized by this strategy. A preliminary mechanism study suggested the carbon-centered radical was involved in the catalytic cycle.
- Xie, Lijuan,Lu, Cong,Jing, Dong,Ou, Xinrui,Zheng, Ke
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p. 3649 - 3653
(2019/06/04)
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- Catalyst-free cyclization of anthranils and cyclic amines: One-step synthesis of rutaecarpine
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An efficient synthesis of a variety of quinazolinone derivatives via a direct cyclization reaction between commercially available anthranils and cyclic amines is described. The developed transformation proceeds with the merits of high step- and atom-efficiency, a broad substrate scope, and good to excellent yields, without additional catalysts, and offers a practical way for the preparation of rutaecarpine and its derivatives with structural diversity.
- Li, Jian,Wang, Zheng-Bing,Xu, Yue,Lu, Xue-Chen,Zhu, Shang-Rong,Liu, Li
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p. 12072 - 12075
(2019/10/14)
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- Synthesis and further transformations of 8-chloro-3,4-dihydroisoquinoline
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Two procedures for the synthesis of barely accessible 8-chloro-3,4-dihydroisoquinoline were investigated. The first approach is based on a directed ortho-lithiation of N-pivaloyl meta-chlorophenylethylamine, followed by formylation and subsequent ring closure under acidic conditions. In the second, more advantageous variant, the N-hydroxyethyl ortho-chlorobenzylamine intermediate undergoes a Friedel-Crafts reaction, and the resulting tetrahydro derivative is oxidized with N-bromosuccinimide. The 8-chloro-3,4-dihydroisoquinoline key intermediate is then applied in Suzuki reactions to give various 8-aryl-3,4-dihydroisoquinolines, which are finally treated with alkyl or aryllithiums to give 1-substituted 8-aryl-1,2,3,4-tetrahydroisoquinolines. These novel 1,2,3,4-tetrahydroisoquinoline derivatives can be used as building blocks in the synthesis of potential drug candidates.
- Hargitai, Csilla,Nagy, Tamás,Halász, Judit,Koványi-Lax, Gy?rgyi,Németh, Gábor,Simig, Gyula,Volk, Balázs
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p. 7009 - 7017
(2018/10/24)
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- Chlorination/cyclodehydration of amino alcohols with SOCl2: An old reaction revisited
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(Chemical Equation Presented) A simple, one-pot preparation of cyclic amines via efficient chlorination of amino alcohols with use of SOCl2 has been developed. This approach obviates the need for the classical N-protection/O-activation/cyclization/deprotection sequence commonly employed for this type of transformation. The reaction pathways and the general scope of this method have also been investigated.
- Xu, Feng,Simmons, Bryon,Reamer, Robert A.,Corley, Edward,Murry, Jerry,Tschaen, David
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p. 312 - 315
(2008/09/17)
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- The influence of substitution at aromatic part of 1,2,3,4-tetrahydroisoquinoline on in vitro and in vivo 5-HT1A/5-HT2A receptor activities of its 1-adamantoyloaminoalkyl derivatives
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Further structure-activity relationship (SAR) studies with the 1,2,3,4-tetrahydroisoquinoline (THIQ) class of 5-HT1A ligands led to the synthesis of new 1-adamantoyloaminoalkyl derivatives. The impact of substituent variations in the aromatic part of THIQ moiety on 5-HT1A and 5-HT2A receptor affinities, as well as in vivo functional properties of the investigated compounds were discussed. It was found that modification reduced the binding affinity for 5-HT1A receptors (in comparison with unsubstituted THIQ derivatives); however, the majority of new compounds still remained potent 5-HT1A ligands (Ki = 4.9-46 nM) and most of them showed features of partial agonists of postsynaptic 5-HT1A receptors. At the same time, their 5-HT2A receptor affinity was slightly increased (Ki = 40-1475 nM), which resulted in a loss of 5-HT2A/5-HT1A selectivity. 5-Br,8-OCH3 derivative - the most potent, mixed 5-HT1A/5-HT2A ligand - produced activation of presynaptic 5-HT1A receptors and showed properties of a 5-HT2A receptor antagonist. Copyright
- Bojarski, Andrzej J,Mokrosz, Maria J,Minol, Sijka Charakchieva,Koziol, Aneta,Wesolowska, Anna,Tatarczynska, Ewa,Klodzinska, Aleksandra,Chojnacka-Wojcik, Ewa
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- Synthesis of Fused Heterocycles: 1,2,3,4-Tetrahydroisoquinolines and Ring Homologues via Sulphonamidomethylation
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The title heterocycles (3) have been obtained by a two-step synthesis; namely an initial intramolecular sulphonamidomethylation of N-aralkylsulphonamides (1) in acid media followed by desulphonylation of compounds (2) under moderate conditions, either by reduction or acid hydrolysis.Generally both steps gave good or high yields of compounds (3) variously substituted in the aromatic ring and with a six-, seven-, or eight-membered heterocyclic ring.
- Orazi, Orfeo O.,Corral, Renee A.,Giaccio, Hector
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p. 1977 - 1982
(2007/10/02)
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- Inhibitors of phenylethanolamine N-methyltransferase and epinephrine biosynthesis: I. Chloro-substituted 1,2,3,4-tetrahydroisoquinolines
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In a search for inhibitors of epinephrine biosynthesis as potential therapeutic agents, a series of 13 ring-chlorinated 1,2,3,4-tetrahydroisoquinolines was prepared. These compounds were tested initially for their ability to inhibit rabbit adrenal phenylethanolamine N-methyltransferase (PNMT) in vitro. Enzyme-inhibitor dissociation constants, determined for the six most potent members of the series, indicated the following order of decreasing potency: 7,8-Cl2>6,7,8-Cl3>7-Cl~8-Cl>5,6,7,8-Cl4>5,7,8-Cl3. These compounds were subsequently examined for PNMT-inhibiting activity in intact rats and mice. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline (SK&F 64139) was the most potent member of the series both in vitro and in vivo and is currently undergoing clinical investigation.
- Bondinell,Chapin,Girard,Kaiser,Krog,Pavloff,Schwartz,Silvestri,Vaidya,Lam,Wellman,Pendleton
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p. 506 - 511
(2007/10/02)
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